Journal article
Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity
Proceedings of the National Academy of Sciences - PNAS, v 95(24), pp 14500-14505
24 Nov 1998
PMID: 9826729
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Abstract
The HIV-1 envelope protein gp120 induces apoptosis in hippocampal neurons. Because chemokine receptors act as cellular receptors for HIV-1, we examined rat hippocampal neurons for the presence of functional chemokine receptors. Fura-2-based Ca imaging showed that numerous chemokines, including SDF-1α, RANTES, and fractalkine, affect neuronal Ca signaling, suggesting that hippocampal neurons possess a wide variety of chemokine receptors. Chemokines also blocked the frequency of spontaneous glutamatergic excitatory postsynaptic currents recorded from these neurons and reduced voltage-dependent Ca currents in the same neurons. Reverse transcription–PCR demonstrated the expression of CCR1, CCR4, CCR5, CCR9/10, CXCR2, CXCR4, and CX
3
CR1, as well as the chemokine fractalkine in these neurons. Both fractalkine and macrophage-derived chemokine (MDC) produced a time-dependent activation of extracellular response kinases (ERK)-1/2, whereas no activation of c-JUN NH
2
-terminal protein kinase (JNK)/stress-activated protein kinase, or p38 was evident. Furthermore, these two chemokines, as well as SDF-1α, activated the Ca- and cAMP-dependent transcription factor CREB. Several chemokines were able also to block gp120-induced apoptosis of hippocampal neurons, both in the presence and absence of the glial feeder layer. These data suggest that chemokine receptors may directly mediate gp120 neurotoxicity.
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Details
- Title
- Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity
- Creators
- Olimpia Meucci - Department of Pharmacological and Physiological Sciences, University of Chicago, 947 E. 58th Street (MC 0926), Chicago, IL 60637; andAlessandro Fatatis - Department of Pharmacological and Physiological Sciences, University of Chicago, 947 E. 58th Street (MC 0926), Chicago, IL 60637; andArthur A Simen - Department of Pharmacological and Physiological Sciences, University of Chicago, 947 E. 58th Street (MC 0926), Chicago, IL 60637; andTrevor J Bushell - Department of Pharmacological and Physiological Sciences, University of Chicago, 947 E. 58th Street (MC 0926), Chicago, IL 60637; andPatrick W Gray - Department of Pharmacological and Physiological Sciences, University of Chicago, 947 E. 58th Street (MC 0926), Chicago, IL 60637; andRichard J Miller - Department of Pharmacological and Physiological Sciences, University of Chicago, 947 E. 58th Street (MC 0926), Chicago, IL 60637; and
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 95(24), pp 14500-14505
- Publisher
- The National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000077191200091
- Scopus ID
- 2-s2.0-0032564406
- Other Identifier
- 991014878159004721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Neurosciences